Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Nucleic acids for inhibiting expression of lpa in a cell

a technology of nucleic acids and lpa, which is applied in the field of nucleic acids for inhibiting the expression of lpa in a cell, can solve the problems of complex process, increased risk of suffering, and severe limitations of nucleic acid silencing trigger discovery, so as to prevent and reduce the risk of suffering

Active Publication Date: 2022-06-02
SILENCE THERAPEUTIC AG
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]The nucleic acid or the composition comprising the nucleic acid or conjugated nucleic acid of the invention may be used in the treatment of a disease, disorder or syndrome. The treatment may be to prevent and reduce risk to suffer from stroke, atherosclerosis, thrombosis or cardiovascular diseases such as coronary heart disease or aortic stenosis and any other disease or pathology associated to elevated levels of Lp(a)-containing particles.DETAILED DESCRIPTION OF THE INVENTION
[0404]In cells and / or subjects treated with or receiving the nucleic acid or conjugated nucleic acid of the present invention, the LPA expression may be inhibited compared to untreated cells and / or subjects by a range from 15% up to 100% but at least about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% or intermediate values. The level of inhibition may allow treatment of a disease associated with LPA expression or overexpression, or may serve to further investigate the functions and physiological roles of the LPA gene product.

Problems solved by technology

According to Watts and Corey in the Journal of Pathology (2012; Vol 226, p 365 379) there are algorithms that can be used to design nucleic acid silencing triggers, but all of these have severe limitations.
Therefore, the discovery of a potent nucleic acid silencing trigger with minimal off target effects is a complex process.
Genetically defined high Lp(a) particle serum levels are unaffected by diet and exercise and are associated to increased risk to suffer from cardiovascular disease through the associated atherosclerotic potential (Alonso et al., Journal of the American College of Cardiology Vol. 63, No. 19, 2014).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Nucleic acids for inhibiting expression of lpa in a cell
  • Nucleic acids for inhibiting expression of lpa in a cell
  • Nucleic acids for inhibiting expression of lpa in a cell

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0437]A number of modified and conjugated siRNA molecules used for functional examples are shown here.

LPA-1038 Derivatives:

[0438]

GalNAc-LPA-1038-L1First strand(SEQ ID NO: 119, based on SEQ ID NO 5)OMeA-(ps)-FU-(ps)-OMeA-FA-OMeC-FU-OMeC-FU-OMeG-FU-OMeC-FC-OMeA-FU-OMeU-FA-OMeC-(ps)-FC-(ps)-OMeA 3′Second strand(SEQ ID NO: 120, based on SEQ ID NO SEQ ID NO 6)5′[ST23 (ps)]3 long trebler (ps)FU-OMeG-FG-OMeU-FA-OMeA-FU-OMeG-FG-OMeA-FC-OMeA-FG-OMeA-FG-OMeU-FU-(ps)-OMeA-(ps)-FU 3′GalNAc-LPA-1038-L6First strand(SEQ ID NO: 121, based on SEQ ID NO 5)OMeA-(ps)-FU-(ps)-OMeA-FA-OMeC-FU-OMeC-FU-OMeG-FU-OMeC-FC-OMeA-FU-OMeU-FA-OMeC-(ps)-FC-(ps)-OMeA 3′Second strand(SEQ ID NO: 122, based on SEQ ID NO 6)5′[ST23 (ps)]3 ST43 (ps)FU-OMeG-FG-OMeU-FA-OMeA-FU-OMeG-FG-OMeA-FC-OMeA-FG-OMeA-FG-OMeU-FU-(ps)-OMeA-(ps)-FU 3′

[0439]FN (N=A, C, G, U) denotes 2′Fluoro, 2′ DeoxyNucleosides

[0440]OMeN (N=A, C, G, U) denotes 2′O Methyl Nucleosides

[0441](ps) indicates a phosphorothioate linkage

[0442]ST23 and ST43 are as b...

example 2

[0453]Screening of non-conjugated siRNA molecules (Table 1) for inhibition of LPA mRNA expression in human RT-4 cells.

[0454]Liposomal transfection complexes were prepared in triplicate at a ratio of 1.5 μl RNAiMax (ThermoFisher) / 80 pmol of the indicated siRNA molecules. The complex was diluted to the indicated concentrations of 2.5 nM and 25 nM, respectively (values represented pairwise as light and darker grey bars). RT4 human urinary bladder transitional cell papilloma cells expressing endogenously LPA were seeded at a density of 125.000 cells per well in 24-well format on top of previously plated transfection complexes (reverse transfection) at the indicated concentration. 24 hours after transfection total RNA was isolated using the Spin Cell Mini Kit 250 (Stratec). LPA mRNA levels were determined by qRT-PCR relative to PPIB mRNA expression in the respective samples as housekeeping transcript. Values were normalized to the amount of LPA mRNA detected in untreated cells (intraplat...

example 3

[0455]Dose response of non-conjugated LPA-targeting siRNA compounds on LPA mRNA expression in human RT-4 cells.

[0456]RT4 human urinary bladder transitional cell papilloma cells were reversely transfected as described above (Example 2) and treated at the indicated concentration (range 100 nM to 0.2 nM) with the different non-conjugated siRNA compounds (Table 1) as labeled. 24 h post transfection, total RNA was isolated using the Spin Cell Mini Kit 250 (Stratec). LPA mRNA levels were determined by qRT-PCR relative to PPIB mRNA expression in the respective samples as housekeeping transcript. Values were normalized to the amount of LPA mRNA detected in untreated cells. The bars represent the remaining LPA mRNA expression for each data point. Results are shown in FIG. 2.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Tmaaaaaaaaaa
Tmaaaaaaaaaa
Tmaaaaaaaaaa
Login to View More

Abstract

The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the LPA gene expression or inhibit its expression, preferably for use as treatment, prevention or reduction of risk of suffering cardiovascular disease such as coronary heart disease or aortic stenosis or stroke or any other disorder, pathology or syndrome linked to elevated levels of Lp(a) particles.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 14 / 293,303, filed May 12, 2021, which is a 35 U.S.C. § 371 national phase entry of International Application No. PCT / EP2019 / 081158, filed Nov. 13, 2019, which claims priority to International Patent Application No. PCT / EP2018 / 081106, filed Nov. 13, 2018, and European Patent Application No. 19174466.3, filed May 14, 2019. The disclosures of each application are hereby incorporated by reference in their entireties.INCORPORATION BY REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY[0002]A Sequence Listing, which is a part of the present disclosure, is submitted concurrently with the specification as a text file. The name of the text file containing the Sequence Listing is “56744A_Seqlisting.txt.” The Sequence Listing was created on Dec. 21, 2021, and is 38,552 bytes in size. The subject matter of the Sequence Listing is incorporated by reference herein in its entirety.FIELD O...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): C12N15/113
CPCC12N15/113C12N2310/14C12N2310/315C12N2310/321C12N2320/30C12N2310/344C12N2310/351C12N2310/53C12N2310/532C12N2310/322A61P9/00A61K31/713C12N2310/11C12N2310/3515C12N2310/3521C12N2310/3533A61K31/7084C12N2310/32
Inventor RIDER, DAVID ANTHONYBETHGE, LUCASFRAUENDORF, CHRISTIANWEINGAERTNER, ADRIENHAUPTMANN, JUDITHDAMES, SIBYLLESCHUBERT, STEFFENTENBAUM, STEPHAN
Owner SILENCE THERAPEUTIC AG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com